Project Summary: Evidence supports a crosstalk between anxiety, emotion and metabolic disease; however, the neural circuits and molecular mechanisms that underlie anxiety and its connection to metabolism are not clear. The lateral hypothalamus (LHA) is a brain region well known for its role in feeding and metabolism, and recent evidence links LHA neurons to classic anxiety circuits. Our new data demonstrates a strong role for a unique population of galanin-expressing (LHA) neurons as modulators of anxiety behavior. We have also previously shown these neurons to drive food reward behaviors. Thus, LHA galanin neurons may provide a crucial link between feeding behavior, metabolism, and emotional status. The goal of this project is to extend the functional LHA galanin circuit by defining the neural circuit inputs and outputs and molecular mechanisms that orchestrate the role of these neurons in anxiety and stress behaviors. We will accomplish this goal through identification of the components of the LHA galanin circuit that are required for regulation of anxiety and testing the dependence of this effect on intact galanin signaling, investigating alternative gene products which may regulate anxiety via LHA galanin neurons, and finally, determine if LHA galanin neurons are targets of the higher order anxiety circuit. The results from this project will reveal mechanisms by which discrete brain regions such as the LHA may influence both emotion and metabolism, providing crucial insight into how dysregulation of emotion and metabolism may interact.